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I. Definition
A. Asthma is a lung disease with the following characteristics: 1) airway obstruction that is reversible, either spontaneously or with treatment; 2) airway inflammation; and 3) increased airway responsiveness to a variety of stimuli.
1. Acute, reversible airflow obstruction
a. >15% increase in FEV1 following inhaled bronchodilator
2. Chronic airway hyperresponsiveness
a. Bronchoprovocation challenge: hyperresponsiveness is defined as >20% fall in FEV1 folio, wing inhaled bronchoconstrictor stimulus, eg, methacholine, histamine, cold dry air, or antigen.
b. Quantification of bronchial hyperresponsiveness: the provocative concentration of a stimulus causing a 20% fall in FEV1 (PC20)
c. The presence of airway hyperresponsiveness is universal in asthma, but its severity varies from person to person and in one individual can vary over time. For instance, it can worsen in response to antigenic exposures ("inciters" of asthma) or improve with allergen avoidance and with certain therapies.
B. Clinical severity of asthma correlates with the severity of bronchial hyperresponsiveness
II. Inflammatory Basis of Airway Hyperresponsiveness
A. Pathologic findings in fatal asthma
1. Submucosa: edema, eosinophilic infiltration, mucous gland hypertrophy, smooth muscle hypertrophy, venodilation
2. Mucosa: edema, eosinophilic infiltration, goblet cell proliferation, desquamation of epithelial lining cells
3. Lumen: mucus, sloughed epithelial cells ("Creola bodies"), eosinophils, Charcot-Leyden crystals, Curschman's spirals
B. Late asthmatic response
1. Following certain allergenic or chemical exposures, delayed airflow obstruction develops several hours after the single exposure: the late asthmatic response.
2. The late asthmatic response is asthma associated with increased numbers of inflammatory cells migrating into the airways and asthma with a period of heightened bronchial hyperresponsiveness (increased over baseline).
C. Direct bronchial biopsies and